Biological models and statistical interactions: an example from multistage carcinogenesis.

From the assessment of statistical interaction between risk factors it is tempting to infer the nature of the biologic interaction between the factors. However, the use of statistical analyses of epidemiologic data to infer biologic processes can be misleading. as an example, we consider the multistage model of carcinogenesis. Under this biologic model, it is shown, by means of simple hypothetical examples, that even if carcinogenic factors act independently, some pairs may fit an additive statistical model, some a multiplicative statistical model, and some neither. The elucidation of biological interactions by means of statistical models requires the imaginative and prudent use of inductive and deductive reasoning; it cannot be done mechanically.